Bacteremia and adrenal gland abscess due to Nocardia cyriacigeorgica: a case report and review

Background Nocardia cyriacigeorgica is one of the most common Nocardia species found in human infections, recently reclassified. Even though Nocardia may affect all organs by hematogenous dissemination, bacteremia are uncommon. Among all possible dissemination sites, the involvement of the adrenal glands is particularly rare. Case presentation We report here a rare case of Nocardia disseminated infection with notably bacteremia and adrenal gland abscess, in a 77-years-old immunocompetent man. Adrenal gland abscess diagnosis was made by imaging (computerized tomography, magnetic resonance and positron emission tomography scan). A complete regression of all lesions including the left adrenal gland was obtained after 6 months of antibiotics. A review of literature was also performed. Conclusion Nocardia bacteremia is a rare event but blood cultures may help to improve detection of Nocardia spp. in a non-invasive way. Adrenal abscess due to Nocardia spp. is very rare with only fourteen cases reported in the literature, but it is a true cause of adrenal masses. Our report suggests that clinician should be aware of this rare location and prioritize a non-invasive diagnosis strategy.


Background
Nocardia is a genus of aerobic actinomycetes and belongs to the family of Nocardiaceae [1]. Bacteria are gram positive, branching, filamentous, and mildly acid-alcohol-fast [1,2]. Nocardia species are ubiquitous, saprophytic and usual component of the soil, water and organic matter [1,2]. Human infections arise mostly by inhalation and sometimes by skin inoculation [1,2]. Currently, 123 Nocardia species are described according to the List of Prokaryotic names with Standing in Nomenclature (http:// www. bacte rio. net), and at least 50 are clinically significant [3]. Thanks to molecular methods (heat shock protein (hsp65) gene, 16 S rRNA gene sequencing), a significant taxonomic changes and species reassignment within the genus were made, particularly among members of the former N. asteroides complex [3]. Nocardia asteroides drug pattern type VI is now known as Nocardia cyriacigeorgica [3]. Thus, it might be difficult for clinicians to understand all the recent changes of Nocardia taxonomy.
Nocardiosis may be localized or disseminated and occur predominately in immunocompromised hosts [1]. The most common infection sites are the lungs, the central nervous system and the skin and soft tissues. All organs may potentially be affected by hematogenous dissemination but Nocardia spp. bacteremia are uncommon Saunier et al. BMC Infectious Diseases (2022) 22:966 [1,4,5] and the involvement of the adrenal glands is particularly rare with only a few cases reported in the literature [6]. We report here a rare case of bacteremia and adrenal gland abscess due to N. cyriacigeorgica. This case is an opportunity to raise awareness of clinicians about the recent change of Nocardia taxonomy, and to review the frequency of bacteremic infection as well as adrenal gland abscesses during Nocardiosis.

Case presentation
A 77-year-old man with no medical history presented for several months a deterioration of his general status with depressive syndrome. In November 2017, he was admitted to the emergency room for respiratory distress. Physical exam revealed the absence of fever, irregular cardiac rate and oxygen saturation at 95% with 9 L of oxygen. Electrocardiogram showed atrial fibrillation. Chest X-ray revealed interstitial syndrome of pulmonary bases. Laboratory investigations revealed leukocytes count 20.4 G/L with 18.60 G/L neutrophils, C-reactive protein 447 mg/L and serum creatinine level 314 µmol/L. He was treated as a severe pneumonia by intravenous levofloxacin (500 mg/12 h) and ceftriaxone (2 g/24 h). The blood pressure fell and the patient was transferred to an intensive care unit where he was intubated because of severe refractory hypoxemia despite high oxygen flow.
A chest CT-scan (computerized tomography) was performed and revealed a diffuse bilateral interstitial syndrome. Five set of blood cultures grew Nocardia cyriacigeorgica in aerobic bottles after respectively 67, 71, 81, 82 and 85 h (blood culture system BD BACTEC FX (Becton Dickinson ® ), identification was done using matrixassisted laser desorption-ionization-time of flight mass spectrometry system (MALDI-TOF MS, Microflex LT, Bruker). Antibiotic susceptibility was determined using agar diffusion assay and ETEST ® technique (bioMérieux), following the CLSI guidelines (https:// clsi. org/). The isolate was susceptible to imipenem, cefotaxime, amikacin, clarithromycin, linezolid, doxycycline, and trimethoprimsulfamethoxazole (TMP-SMX). It was non-susceptible to amoxicillin, ciprofloxacin and amoxicillin-clavulanic acid (intermediate). A diagnosis of disseminated Nocardiosis was subsequently made and antibiotic regimen was changed to linezolid (600 mg/12 h), cefotaxime (2 g/4 h) and amikacin (1.5 g/24 h). As the patient continued to work in the construction industry, we supposed that the source of Nocardiosis was probably by inhalation.
A cerebral CT-scan was performed and revealed bilateral lesions with circumferential contrast enhancement and edema. The biggest lesion (13 mm) was in the right occipital lobe. A chest, abdomen and pelvis (C.A.P) CTscan showed a left adrenal poly-lobed nodular hypertrophy of 57 × 33 × 62 mm (Fig. 1)

. A Positron Emission
Tomography scanner was also made, showing hypermetabolic left adrenal lesion (standardized uptake value (SUV) max = 14), pulmonary hypermetabolism in bilateral postero-basal regions and pleural effusions (SUV max = 4.3), and no other suspect lesion. An abdominal magnetic resonance imaging (MRI) was performed to help distinguishing the nature of this adrenal hypertrophy (Fig. 1). The lesion was clearly in favor of a left adrenal abscess because of the MRI characteristic and the size regression of the lesion under antimicrobial treatment. Transthoracic and trans-esophageal echocardiography showed no sign of endocarditis. HIV serology was negative but a CD4+ T lymphopenia (402 cell/µL or 38%) was observed. Serum protein electrophoresis revealed a normal rate of gamma globulin (10 g/L) with no monoclonal spike. The patient was not diabetic.
Gradually, the patient's clinical condition improved and two weeks after admission, he was transferred to the infectious disease department. Antibiotic treatment was changed to TMP-SMX (4.8 g/960 mg/24 h) and cefotaxime (12 g/24 h for one week and then 9 g/24 h). Nineteen days after beginning these antibiotics, the patient developed skin rash, justifying stopping TMP-SMX and replacing it by clarithromycin (1.5 g/24 h). Six weeks after the beginning of the antibiotic treatment (December 16th, 2017), the patient has recovered, cefotaxime was replaced by ceftriaxone (4 g/24 h) and he returned home. After three months of antibiotic treatment (February 5th, 2018), ceftriaxone was changed to doxycycline (200 mg/24 h) but still combined with clarithromycin (1.5 g/24 h). A C.A.P and brain CT scan were performed after six months of treatment (April 23th, 2018) and showed a complete regression of all lesions including the left adrenal gland with restitution ad integrum and antibiotics were discontinued (Fig. 1).

Discussion and conclusion
We report here a rare case of Nocardia cyriacigeorgica disseminated infection in a non-immunocompromised man with notably a bacteremia and an adrenal gland abscess. The species involved in this case was not a new species as firstly suspected by Yassin et al. [7], nor an emerging pathogen, but in fact, N. cyriacigeorgica and N. asteroides drug pattern type VI belong to the same species [8]. It is no longer appropriate to mention the Nocardia asteroides complex and its six «drug pattern type» whom now are six different taxa: N. abscessus (drug pattern I), N. brevicatena /N. paucivorans (drug pattern II), N. nova complex (drug pattern III), N. transvalensis complex (drug pattern IV), N. farcinica (drug pattern V) and N. cyriacigeorgica (drug pattern VI) [3]. Thus, the main Nocardia species isolated in the majority of human infections are part of the former N. asteroides complex : N. farcinica, N. abscessus, N. cyriacigeorgica, and N. nova [4,9,10] including cases reported prior to the availability of molecular tests [3,8]. In our case, N. cyriacigeorgica was identified by MALDI-TOF MS. Although progress is still needed for the identification of uncommon species, MALDI-TOF MS is a valuable aid for more accurate and rapid identification of Nocardia species [3]. This easier identification probably helps physicians to be more familiar to the complexity of Nocardia taxonomy [3].
Even though Nocardia species can grow in a variety of blood culture media, bacteremia during Nocardiosis is rarely reported [5]. We reviewed large series of Nocardia   [10][11][12][13][14][15][16][17] and found that bacteremia frequency range from 3.7 to 26.5% with a mean value of 10,1%. The study reporting the higher rate of bacteremia (26.5%) included mainly immunocompromised patients with 50% of disseminated forms [10]. Blood cultures seem then useful in the diagnosis of Nocardiosis. In the review of Kontoyiannis et al. [5], the isolation of Nocardia in blood culture preceded the isolation from other sites in 44% (8/18) of cases and blood cultures were the only source of diagnostic material in one-fourth of the cases (9/36). Thus, detection of N. cyriacigeorgica in blood cultures allowed a quick diagnosis and accurate treatment that probably improved the prognosis of our patient. Low bacteremia frequency during Nocardia could be explained by a too short incubation time of blood cultures, a co-infection with more resilient organisms (as Gram-negative bacteria), an infrequent and intermittent bacteremia or an empiric treatment with good activity against Nocardia [5,18]. Nowadays, usual blood culture media allows the detection of Nocardia spp., although specific media increase detection of Nocardia spp. such as biphasic brain-heart infusion or Castañeda media. In our case, the bacteremia was detected using BD BAC-TEC FX (Becton Dickinson ® ). The growth of bacteria on usual blood culture probably increases the diagnosis of bacteremia in this infection. To increase awareness about Nocardia infections in microbiology laboratories and to improve the yield of cultures for Nocardia, it may be advisable to increase duration of incubation and perform subcultures on to blood agar from the broth [5,18].
Hematogenous dissemination of Nocardiosis can affect all organs, but some are rarely involved such as the adrenal glands. Only fourteen cases of Nocardia adrenal abscesses are reported in the literature. Adrenal abscesses are caused by N. farcinica (7/14), N. asteroides (4/14) and N. beijingensis (1/14) (see Table 1) [6,10,11,[19][20][21][22]. N. cyriacigeorgica is involved in only two cases [19,21]. Adrenal masses are benign or malignant tumours most of the time but infectious causes (abscesses) must also be considered [6]. Disseminated Nocardiosis with adrenal abscesses can masquerading as malignant disease and commonly leading to an invasive strategy (puncture, laparoscopic drainage, adrenalectomy) to make a diagnosis and can lead to injury (see Table 1) [6,10,11,[19][20][21][22]. In our case, the presence of bacteremia, the use of medical imaging and biology and the evolution under treatment (lesion with progressive regression and restitution ad integrum after 6 months of antibiotic regimen) helped us to confirm infectious nature of the adrenal mass. Among the cases of Nocardia adrenal abscess [6,10,11,[19][20][21][22], seven were associated with bacteremia (7/14 i.e. 50%) [6,10,11,19,20,23,24] and only one did not underwent an invasive procedure for diagnosis [23]. Furthermore, in a recent similar case, the patient underwent adrenalectomy and blood cultures taken 3 days prior to surgery grew N. cyriacigeorgica [21]. When we face an adrenal tumour with associated lesions (lung, brain etc.), it is therefore important to take time and promote non-invasive strategies such as medical imaging and biology (blood cultures particularly) to make a diagnosis. Moreover, even if some authors suggested that draining abscess collection is crucial to a successful outcome [5], in our case, a strategy with antibiotic regimen only was successful.
In conclusion, the Nocardia spp. taxonomy underwent many changes in recent years and despite complexity, knowledge of most common species is needed. Nocardia bacteremia is a rare event but blood cultures may help to improve detection of Nocardia spp. in a non-invasive way. Despite Nocardia spp. adrenal abscess being very rare with only fourteen cases reported, it is a true cause of adrenal masses. Our report suggests that clinician should be aware of this rare location and prioritize a noninvasive strategy.